U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Hawkinsinuria(HWKS)

MedGen UID:
419319
•Concept ID:
C2931042
•
Disease or Syndrome
Synonym: 4-Alpha-hydroxyphenylpyruvate hydroxylase deficiency
SNOMED CT: Hawkinsinuria (414380008)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal dominant inheritance (Orphanet)
 
Gene (location): HPD (12q24.31)
 
HPO: HP:0034457
Monarch Initiative: MONDO:0007700
OMIM®: 140350
Orphanet: ORPHA2118

Definition

Hawkinsinuria (HWKS) is an autosomal dominant inborn error of metabolism. Metabolic acidosis and tyrosinemia are transient, and symptoms improve within the first year of life. Patients continue to excrete the hawkinsin metabolite in their urine throughout life (Danks et al., 1975; Tomoeda et al., 2000). [from OMIM]

Clinical features

From HPO
4-Hydroxyphenylpyruvic aciduria
MedGen UID:
376416
•Concept ID:
C1848678
•
Finding
Increased relative concentration of 4-hydroxyphenylpyruvic acid in the urine.
See: Feature record | Search on this feature
4-hydroxyphenylacetic aciduria
MedGen UID:
376417
•Concept ID:
C1848680
•
Finding
Increased concentration of 4-hydroxyphenylacetic acid in the urine.
See: Feature record | Search on this feature
Hawkinsinuria
MedGen UID:
419319
•Concept ID:
C2931042
•
Disease or Syndrome
Hawkinsinuria (HWKS) is an autosomal dominant inborn error of metabolism. Metabolic acidosis and tyrosinemia are transient, and symptoms improve within the first year of life. Patients continue to excrete the hawkinsin metabolite in their urine throughout life (Danks et al., 1975; Tomoeda et al., 2000).
See: Feature record | Search on this feature
Failure to thrive
MedGen UID:
746019
•Concept ID:
C2315100
•
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
See: Feature record | Search on this feature
Intellectual disability, mild
MedGen UID:
10044
•Concept ID:
C0026106
•
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
See: Feature record | Search on this feature
Restlessness
MedGen UID:
854457
•Concept ID:
C3887611
•
Sign or Symptom
A state of unease is characterized by diffuse motor activity or motion, which is subject to limited control, nonproductive, or disorganized behavior.
See: Feature record | Search on this feature
Microcephaly
MedGen UID:
1644158
•Concept ID:
C4551563
•
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
See: Feature record | Search on this feature
Metabolic acidosis
MedGen UID:
65117
•Concept ID:
C0220981
•
Pathologic Function
Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause.
See: Feature record | Search on this feature
Hypertyrosinemia
MedGen UID:
742296
•Concept ID:
C1879362
•
Disease or Syndrome
An increased concentration of tyrosine in the blood.
See: Feature record | Search on this feature
Sparse hair
MedGen UID:
1790211
•Concept ID:
C5551005
•
Finding
Reduced density of hairs.
See: Feature record | Search on this feature
Show allHide all

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHawkinsinuria
Follow this link to review classifications for Hawkinsinuria in Orphanet.

Conditions with this feature

Hawkinsinuria
MedGen UID:
419319
•Concept ID:
C2931042
•
Disease or Syndrome
Hawkinsinuria (HWKS) is an autosomal dominant inborn error of metabolism. Metabolic acidosis and tyrosinemia are transient, and symptoms improve within the first year of life. Patients continue to excrete the hawkinsin metabolite in their urine throughout life (Danks et al., 1975; Tomoeda et al., 2000).
See: Condition Record
Hawkinsinuria

Professional guidelines

PubMed

Product analysis and inhibition studies of a causative Asn to Ser variant of 4-hydroxyphenylpyruvate dioxygenase suggest a simple route to the treatment of Hawkinsinuria.
Brownlee JM, Heinz B, Bates J, Moran GR
Biochemistry 2010 Aug 24;49(33):7218-26. doi: 10.1021/bi1008112. PMID: 20677779

Recent clinical studies

Etiology

Evaluation of comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry for the diagnosis of inherited metabolic disorders using an automated data processing strategy.
Wojtowicz P, Zrostlíková J, Kovalczuk T, Schůrek J, Adam T
J Chromatogr A 2010 Dec 17;1217(51):8054-61. Epub 2010 Oct 1 doi: 10.1016/j.chroma.2010.09.067. PMID: 20961553
Long-term follow up of a new case of hawkinsinuria.
Lehnert W, Stögmann W, Engelke U, Wevers RA, van den Berg GB
Eur J Pediatr 1999 Jul;158(7):578-82. doi: 10.1007/s004310051151. PMID: 10412819

Diagnosis

Variant analysis of HPD genes from two families showing elevated tyrosine upon newborn screening by tandem mass spectrometry (MS/MS).
Zhao D, Tian Y, Li X, Ni M, Zhu X, Jia L
J Pediatr Endocrinol Metab 2020 Apr 28;33(4):563-567. doi: 10.1515/jpem-2019-0498. PMID: 32109208
Hawkinsinuria clinical practice guidelines: a Mexican case report and literature review.
Cruz-Camino H, Vazquez-Cantu DL, Zea-Rey AV, López-Valdez J, Jiménez-Lozano J, Gómez-Gutiérrez R, Cantú-Reyna C
J Int Med Res 2020 Feb;48(2):300060519863543. Epub 2019 Jul 25 doi: 10.1177/0300060519863543. PMID: 31342835Free PMC Article
Qualitative urinary organic acid analysis: 10 years of quality assurance.
Peters V, Bonham JR, Hoffmann GF, Scott C, Langhans CD
J Inherit Metab Dis 2016 Sep;39(5):683-687. Epub 2016 May 4 doi: 10.1007/s10545-016-9941-1. PMID: 27146437
Hawkinsinuria in two unrelated Greek newborns: identification of a novel variant, biochemical findings and treatment.
Thodi G, Schulpis KH, Dotsikas Y, Pavlides C, Molou E, Chatzidaki M, Triantafylli O, Loukas YL
J Pediatr Endocrinol Metab 2016 Jan;29(1):15-20. doi: 10.1515/jpem-2015-0132. PMID: 26226126
Long-term follow up of a new case of hawkinsinuria.
Lehnert W, Stögmann W, Engelke U, Wevers RA, van den Berg GB
Eur J Pediatr 1999 Jul;158(7):578-82. doi: 10.1007/s004310051151. PMID: 10412819

Therapy

Expanding the phenotype of hawkinsinuria: new insights from response to N-acetyl-L-cysteine.
Gomez-Ospina N, Scott AI, Oh GJ, Potter D, Goel VV, Destino L, Baugh N, Enns GM, Niemi AK, Cowan TM
J Inherit Metab Dis 2016 Nov;39(6):821-829. Epub 2016 Aug 3 doi: 10.1007/s10545-016-9963-8. PMID: 27488560

Prognosis

Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria.
Tomoeda K, Awata H, Matsuura T, Matsuda I, Ploechl E, Milovac T, Boneh A, Scott CR, Danks DM, Endo F
Mol Genet Metab 2000 Nov;71(3):506-10. doi: 10.1006/mgme.2000.3085. PMID: 11073718
Long-term follow up of a new case of hawkinsinuria.
Lehnert W, Stögmann W, Engelke U, Wevers RA, van den Berg GB
Eur J Pediatr 1999 Jul;158(7):578-82. doi: 10.1007/s004310051151. PMID: 10412819

Clinical prediction guides

Product analysis and inhibition studies of a causative Asn to Ser variant of 4-hydroxyphenylpyruvate dioxygenase suggest a simple route to the treatment of Hawkinsinuria.
Brownlee JM, Heinz B, Bates J, Moran GR
Biochemistry 2010 Aug 24;49(33):7218-26. doi: 10.1021/bi1008112. PMID: 20677779
Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria.
Tomoeda K, Awata H, Matsuura T, Matsuda I, Ploechl E, Milovac T, Boneh A, Scott CR, Danks DM, Endo F
Mol Genet Metab 2000 Nov;71(3):506-10. doi: 10.1006/mgme.2000.3085. PMID: 11073718

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Reviews

    Related information

    • ClinVar
      Related medical variations
    • Gene
      Related information in NCBI Gene
    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • MeSH
      Related Medical Subject Headings
    • OMIM
      Related records in OMIM
    • OMIM(Genes)
      OMIM records containing genes associated with phenotypes registered in MedGen
    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed
    • PubMed (OMIM)
      Related literature resources in PubMed

    Recent activity

    Clear Turn Off Turn On

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...